Designing multi-epitope mRNA construct as a universal influenza vaccine candidate for future epidemic/pandemic preparedness.

Despite the availability of prevention and treatment strategies and advancing immunization approaches, the influenza virus remains a global threat that continues to plague humanity with unpredictable pandemics. Due to the unusual genetic variability and segmented genome, the reassortment between different strains of influenza is facilitated and the viruses continuously evolve and adapt to the host cell's immunity. This underlies the seasonal vaccine mismatches that decrease the vaccine efficacy and increase the risk of outbreaks. Thus, the development of a universal vaccine covering all the influenza A and B strains would reduce the pervasiveness of the influenza virus. In the current study, a potentially universal influenza multi-epitope vaccine was designed based on the experimentally tested conserved T cell and B cell epitopes of hemagglutinin (HA), neuraminidase (NA), nucleoprotein (NP), and matrix-2 proton channel (M2) of the virus. The immune simulation and molecular docking of the vaccine construct with TLR2, TLR3, and TLR4 elicited the favorable immunogenicity of the vaccine and the formation of stable complexes, respectively. Ultimately, based on the immunoinformatics analysis, the universal mRNA multi-epitope vaccine designed in this study might have a protection potential against the various subtypes of influenza A and B.

Self-Amplifying RNA Approach for Protein Replacement Therapy.

Messenger RNA (mRNA) technology has already been successfully tested preclinically and there are ongoing clinical trials for protein replacement purposes; however, more effort has been put into the development of prevention strategies against infectious diseases. Apparently, mRNA vaccine approval against coronavirus disease 2019 (COVID-19) is a landmark for opening new opportunities for managing diverse health disorders based on this approach. Indeed, apart from infectious diseases, it has also been widely tested in numerous directions including cancer prevention and the treatment of inherited disorders. Interestingly, self-amplifying RNA (saRNA)-based technology is believed to display more developed RNA therapy compared with conventional mRNA technique in terms of its lower dosage requirements, relatively fewer side effects, and possessing long-lasting effects. Nevertheless, some challenges still exist that need to be overcome in order to achieve saRNA-based drug approval in clinics. Hence, the current review discusses the feasibility of saRNA utility for protein replacement therapy on various health disorders including rare hereditary diseases and also provides a detailed overview of saRNA advantages, its molecular structure, mechanism of action, and relevant delivery platforms.

Strategy of developing nucleic acid-based universal monkeypox vaccine candidates.

Until May 2022, zoonotic infectious disease monkeypox (MPX) caused by the monkeypox virus (MPXV) was one of the forgotten viruses considered to be geographically limited in African countries even though few cases outside of Africa were identified. Central and West African countries are known to be endemic for MPXV. However, since the number of human MPX cases has rapidly increased outside of Africa the global interest in this virus has markedly grown. The majority of infected people with MPXV have never been vaccinated against smallpox virus. Noteworthily, the MPXV spreads fast in men who have sex with men (MSM). Preventive measures against MPXV are essential to be taken, indeed, vaccination is the key. Due to the antigenic similarities, the smallpox vaccine is efficient against MPXV. Nevertheless, there is no specific MPXV vaccine until now. Nucleic acid vaccines deserve special attention since the emergency approval of two messenger RNA (mRNA)-based coronavirus disease 2019 (COVID-19) vaccines in 2020. This milestone in vaccinology has opened a new platform for developing more mRNA- or DNA-based vaccines. Certainly, this type of vaccine has a number of advantages including time- and cost-effectiveness over conventional vaccines. The platform of nucleic acid-based vaccines gives humankind a huge opportunity. Ultimately, there is a strong need for developing a universal vaccine against MPXV. This review will shed the light on the strategies for developing nucleic acid vaccines against MPXV in a timely manner. Consequently, developing nucleic acid-based vaccines may alleviate the global threat against MPXV.

Promising strategy for developing mRNA-based universal influenza virus vaccine for human population, poultry, and pigs- focus on the bigger picture.

Since the first outbreak in the 19th century influenza virus has remained emergent owing to the huge pandemic potential. Only the pandemic of 1918 caused more deaths than any war in world history. Although two types of influenza- A (IAV) and B (IBV) cause epidemics annually, influenza A deserves more attention as its nature is much wilier. IAVs have a large animal reservoir and cause the infection manifestation not only in the human population but in poultry and domestic pigs as well. This many-sided characteristic of IAV along with the segmented genome gives rise to the antigenic drift and shift that allows evolving the new strains and new subtypes, respectively. As a result, the immune system of the body is unable to recognize them. Importantly, several highly pathogenic avian IAVs have already caused sporadic human infections with a high fatality rate (~60%). The current review discusses the promising strategy of using a potentially universal IAV mRNA vaccine based on conserved elements for humans, poultry, and pigs. This will better aid in averting the outbreaks in different susceptible species, thus, reduce the adverse impact on agriculture, and economics, and ultimately, prevent deadly pandemics in the human population.

Development of an LNP-Encapsulated mRNA-RBD Vaccine against SARS-CoV-2 and Its Variants.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is undoubtedly the most challenging pandemic in the current century and remains a global health emergency. As the number of COVID-19 cases in the world is on the rise and variants continue to emerge, there is an urgent need for vaccines. Among all immunization approaches, mRNA vaccines have demonstrated more promising results in response to this challenge. Herein, we designed an mRNA-based vaccine encoding the receptor-binding domain (RBD) of SARS-CoV-2 encapsulated in lipid nanoparticles (LNPs). Intramuscular (i.m.) administration of the mRNA-RBD vaccine elicited broad-spectrum neutralizing antibodies and cellular responses against not only the wild-type SARS-CoV-2 virus but also Delta and Omicron variants. These results indicated that two doses of mRNA-RBD immunization conferred a strong immune response in mice against the wild-type SARS-CoV-2, while the booster dose provided a sufficient immunity against SARS-CoV-2 and its variants. Taken together, the three-dose regimen strategy of the mRNA-RBD vaccine proposed in the present study appears to be a promising reference for the development of mRNA vaccines targeting SARS-CoV-2 variants.

Development of an LNP-Encapsulated mRNA-RBD Vaccine against SARS-CoV-2 and Its Variants

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is undoubtedly the most challenging pandemic in the current century and remains a global health emergency. As the number of COVID-19 cases in the world is on the rise and variants continue to emerge, there is an urgent need for vaccines. Among all immunization approaches, mRNA vaccines have demonstrated more promising results in response to this challenge. Herein, we designed an mRNA-based vaccine encoding the receptor-binding domain (RBD) of SARS-CoV-2 encapsulated in lipid nanoparticles (LNPs). Intramuscular (i.m.) administration of the mRNA-RBD vaccine elicited broad-spectrum neutralizing antibodies and cellular responses against not only the wild-type SARS-CoV-2 virus but also Delta and Omicron variants. These results indicated that two doses of mRNA-RBD immunization conferred a strong immune response in mice against the wild-type SARS-CoV-2, while the booster dose provided a sufficient immunity against SARS-CoV-2 and its variants. Taken together, the three-dose regimen strategy of the mRNA-RBD vaccine proposed in the present study appears to be a promising reference for the development of mRNA vaccines targeting SARS-CoV-2 variants.

Development of DNA Vaccine Candidate against SARS-CoV-2.

Despite the existence of various types of vaccines and the involvement of the world's leading pharmaceutical companies, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains the most challenging health threat in this century. Along with the increased transmissibility, new strains continue to emerge leading to the need for more vaccines that would elicit protectiveness and safety against the new strains of the virus. Nucleic acid vaccines seem to be the most effective approach in case of a sudden outbreak of infection or the emergence of a new strain as it requires less time than any conventional vaccine development. Hence, in the current study, a DNA vaccine encoding the trimeric prefusion-stabilized ectodomain (S1+S2) of SARS-CoV-2 S-protein was designed by introducing six additional prolines mutation, termed HexaPro. The three-dose regimen of designed DNA vaccine immunization in mice demonstrated the generation of protective antibodies.